Department of Biomedical Engineering, Northwestern University, 2145 Sheridan Road, Tech E310, Evanston, Illinois, 60208, USA.
Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
Pharm Res. 2017 Oct;34(10):2163-2171. doi: 10.1007/s11095-017-2224-1. Epub 2017 Aug 2.
Design of intravaginal rings (IVRs) for delivery of antiretrovirals is often guided by in vitro release under sink conditions, based on the assumption that in vivo release will follow a similar release profile.
We conducted a dose-ranging study in the female reproductive tract of pigtail macaques using matrix IVRs containing IQP-0528, a poorly soluble but highly potent antiretroviral drug with an IC of 146 ng/mL. These IVRs consisted of drug-loaded segments, 15.6% IQP-0528 in Tecoflex 85A, comprising either all, half, or a quarter of the entire ring.
In vitro release under sink conditions demonstrates loading-proportional release, with a cumulative 30-day release of 48.5 ± 2.2 mg for our 100% loaded ring, 24.8 ± .36 mg from our 50% loaded ring, and 13.99 ± 1.58 mg from our 25% loaded ring. In vivo, while drug concentration in vaginal fluid is well in excess of IQP-0528's EC, we find no statistical difference between the different ring loadings in either swab drug levels or drug released from our rings.
We show that in vitro release may not accurately reflect in vivo release, particularly for poorly soluble drugs. All tested loadings of our IVRs are capable of delivering IQP-0528 well in excess of the IC.
阴道环（IVR）的设计通常基于在体外条件下的药物释放情况，假设体内释放将遵循类似的释放曲线。
我们在雌性恒河猴的生殖道中进行了一项剂量范围研究，使用含有 IQP-0528 的基质 IVR，IQP-0528 是一种水溶性差但具有高活性的抗逆转录病毒药物，其 IC 为 146ng/mL。这些 IVR 由载药段组成，15.6%的 IQP-0528 装载于 Tecoflex 85A 中，载药量分别为整个环的全部、一半或四分之一。
在体外条件下的药物释放研究中，释放量与载药量成正比，100%载药量的 IVR 在 30 天内累积释放 48.5±2.2mg，50%载药量的 IVR 释放 24.8±0.36mg，25%载药量的 IVR 释放 13.99±1.58mg。在体内，尽管阴道液中的药物浓度远高于 IQP-0528 的 EC，但我们发现不同载药量的 IVR 在拭子药物水平或从 IVR 中释放的药物方面没有统计学差异。
我们表明，体外释放情况可能无法准确反映体内释放情况，尤其是对于水溶性差的药物。我们的 IVR 的所有测试载药量都能够以超过 IC 的剂量释放 IQP-0528。
